The purpose of this study was to evaluate the efficacy of maternal digoxin administration in 16 cases of fetal supraventricular tachyarrhythmia diagnosed by fetal echocardiography; cardiac anatomy was normal in all cases. The retrospective analysis included nine mothers who received digoxin orally in most cases, with control of the arrhythmia in two fetuses. The addition of amiodarone (five cases) and propranolol (two cases) yielded two successes with amiodarone. The therapeutic regimen of digoxin was then modified on the basis of poor response to orally administered digoxin. In the prospective study, digoxin was administered intravenously to seven mothers according to a standard protocol; high doses (1 to 2 mg intravenously) were prescribed for the first 24 hours and intravenous digoxin therapy was maintained for at least 5 days, depending on the fetal response. Digoxin pharmacokinetic studies of four mothers showed an increased plasma clearance and reduced elimination half-life. Digoxin controlled the five supraventricular tachycardias (with hydrops in four cases). Maternal flecainide therapy restored sinus rhythm in two cases of atrial flutter. Our prospective study emphasizes the efficacy and safety for the fetus and the mother of intravenously administered digoxin as a first-choice drug in the treatment of supraventricular tachyarrhythmias. Flecainide may be a promising second-choice drug but requires further clinical investigation. Amiodarone and propranolol seem to be ineffective.